Project Summary Significance: Compared to heterosexual women, lesbian/gay and bisexual (LGB) women report higher rates of physical health problems. Current evidence, which is largely based on self-report, suggests that important health disparities exist in conditions with high rates of morbidity and mortality (e.g., diabetes, heart disease). To date, however, no study has tested differences in objective measures of health risks between LGB and heterosexual women in a representative sample of young adults. We aim to fill this gap by examining putative health disparities using rigorous objective biomarkers of health (i.e. cardiometabolic functioning and inflammation) in young adulthood in a representative, racially diverse sample of young women who are participating in an ongoing longitudinal study, the Pittsburgh Girls Study (PGS) (Aim 1). We will link prospectively gathered data on discrimination stress and childhood adversity to determine the role of stress exposure in the association between sexual minority status and early adult health (Aim 2). Finally, we will test whether health promotion during adolescence attenuates the association between discrimination stress and health risks among LGB women (Aim 3). Approach: Our plan is to leverage comprehensive, prospectively collected data from the PGS and measure current health indicators among LGB women in the PGS (n=230) and a demographic frequency matched sample of heterosexual women (n=230) in early adulthood (ages 22-25 years). Assessments of health will include: waist circumference, blood pressure, lipids, cholesterol, fatty acids, glucose, insulin, proinflammatory cytokines (IL-6; TNF-?), and C-reactive protein. We propose to assess discrimination stress via cortisol and heart rate reactivity to a lab- based discrimination stressor and perceived discrimination experiences measured annually and prospectively from ages 15 to 21 years. Childhood adversity (family stress, trauma, abuse, and peer victimization) has been assessed annually for in the PGS from youth and caregiver reports. Physical and emotional health promotion during adolescence has been assessed in a number of ways in the PGS including vaccine uptake, safe sexual practices, and physical activity, supportive adult presence, and will be complemented by interviews on school climate and coming out experiences. Investigators: Dr. Kathryn Keenan is the Principal Investigator, Drs. Alison Hipwell, Stephanie Stepp, Karen Matthews, Alicia Matthews and Alida Bouris are Co-Investigators, and Ms. Kristen Wroblewski is the biostatistician. Dr. Constance Hammen is the consultant. The investigators have led many successful NIH-funded studies and represent expertise in developmental psychopathology, women's mental health, sexual minority physical and mental health, health psychology, and biostatistics. Collectively, the investigators have experience in administering the TSST to vulnerable populations, measuring cortisol reactivity, and testing hypotheses involving cardiometabolic and inflammatory functioning. Environment: This proposal builds on long-standing, productive collaborations among investigators at the Universities of Chicago, Illinois, and Pittsburgh. Innovation/Impact: The proposed study provides an unprecedented opportunity to explore health disparities in LGB women in a rigorous manner, examine potential mechanisms by which sexual orientation confers health risks, and identify protective factors in a representative and racially diverse sample of LGB and heterosexual women.